Glutamic acid acts as a neurotransmitter in the central nervous system of mammals, and controls the activity of neurocytes or the release of neurotransmitters via a glutamate receptor existing in synapses. At present, a glutamate receptor is classified into an “ionotropic glutamate receptor” and a “metabotropic glutamate receptor” from many pharmacological and biological studies (Hollmann M. and Heinemann S., Annu. Rev. Neurosci., 17 (1994) 31-108). An NMDA (N-methyl-D-aspartate) receptor is an ion-channel glutamate receptor specifically sensitive to the agonist NMDA (Moriyoshi K. et al., Nature, 354 (1991) 31-37; Meguro H. et al., Nature, 357 (1992) 70-74); and this has high Ca2+ permeability (Iino M. et al., J. Physiol., 424 (1990) 151-165). The NMDA receptor is expressed with a specific pattern in a central nervous system (Ozawa S. et al., Prog. Neurobiol., 54 (1998) 581-618).
From many pharmacological and biological studies, it is believed that an NMDA receptor may participate in high-order neurologic functions such as memory and learning (Morris R G., et al., Nature, 319 (1986) 774-776; Tsien J Z. et al., Cell, 87 (1996) 1327-1338). On the other hand, it is suggested that the acute or chronic NMDA receptor hyperactivity or hypoactivity may participate in various nervous system diseases, for example, ischemic apoplexy, hemorrhagic brain injury, traumatic brain injury, neurodegenerative disorders (e.g., Alzheimer's disease, cerebrovascular dementia, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis), glaucoma, AIDS encephalopathy, dependence, schizophrenia, depression, mania, stress-related diseases, epilepsy, and pain (Beal M F., FASEB J., 6 (1992) 3338-3344; Heresco-Levy U. and Javitt D C., Euro. Neuropsychopharmacol., 8 (1998) 141-152; Hewitt D J., Clin. J. Pain, 16 (2000) S73-79). Accordingly, drugs capable of controlling the activity of an NMDA receptor would be extremely useful in clinical application.
As drugs capable of controlling the activity of an NMDA receptor, a large number of non-competitive NMDA receptor antagonists are reported, but many of them have not been used in clinical application because of their side effects based on the NMDA receptor-antagonizing effect thereof, for example, mental aberration such as hallucination or confusion, and giddiness. Some of already-existing NMDA receptor antagonists, for example, ketamine and dextromethorphan have been tried against pain in clinical application (Fisher K. et al., J. Pain Symptom Manage., 20 (2000) 358-373), but the safety margin in the treatment with them is narrow, and their clinical use is limitative (Eide P K., et al., Pain, 58 (1994) 347-354). Memantine is known as a non-competitive NMDA receptor antagonist that has comparatively few side effects (Parsons C G., et al., Neuropharmacol., 38 (1999) 735-767); and recently, it has been reported that this may be effective for Alzheimer's disease (Reisberg B., et al., N. Engl. J. Med., 348 (2003) 1333-1341). However, the safety margin of memantine as a medicine is still not satisfactory, and an NMDA receptor antagonist having a broader safety margin is desired (Ditzler K., Arzneimittelforschung, 41 (1991) 773-780; Maier C., et al., Pain, 103 (2003) 277-283; Riederer P., et al., Lancet, 338 (1991) 1022-1023). It is expected that creation of such an NMDA receptor antagonist having a broader safety margin may bring about new clinical usefulness of the NMDA receptor antagonist.
Patent Document 1 describes a pharmaceutical composition for preventing and treating cerebral ischemia, which comprises an adamantane derivative represented by the following general formula or its pharmaceutically acceptable acid-addition salt:

(wherein R1 and R2 are the same or different, and each represent hydrogen, a linear or branched alkyl group having 1 to 6 carbon atoms, or the like; R3 and R4 are the same or different, and each represent hydrogen, an alkyl group having 1 to 6 carbon atoms, or the like; and R5 represents hydrogen or a linear or branched alkyl group having 1 to 6 carbon atoms. See the official gazette for other symbols in the formula).
In Patent Document 1, the above-mentioned memantine is described as Test Compound No. 1 (memantine is a compound of the formula wherein R1, R2 and R3 are hydrogen atoms, and R4 and R5 are methyl).
Furthermore, Patent Document 2 describes 1-amino-alkylcyclohexane represented by the following general formula as an NMDA receptor antagonist.

(wherein R* is —(CH2)n—(CR6R7)m—NR8R9; n+m=0, 1 or 2; R1 to R9 are each independently selected from a group consisting of a hydrogen atom and C1-6 lower alkyl; and at least R1, R4 and R5 are lower alkyl. See the official gazette for other symbols in the formula).
Furthermore, the present Applicant reports a cyclic amine derivative represented by the following general formula, as an NMDA receptor antagonist in Patent Document 3.

(wherein A represents a 5- to 8-membered cyclic amine optionally having a double bond, optionally having a bridge structure and optionally having substituents of R7 to R11 in the ring, —NH2, —NH(lower alkyl), or —N(lower alkyl)2; ring B represents benzene, thiophene, furan, pyrrole, a 5- to 7-membered cycloalkane, or 5- to 7-membered cycloalkene; X1 represents a bond, a lower alkylene, or -L3-D-L4-; and Y1 represents —OH, —O-lower alkyl, —NH2, or —N3. See the official gazette for other symbols in the formula).
In addition, Patent Document 4 describes 1-aminoindane represented by the following general formula as a therapeutic agent for Parkinson's disease, and the like.

(wherein R1 and R2 independently represent hydrogen, hydroxy, alkyl, alkoxy, or the like; R3 represents hydrogen, alkyl, hydroxy, alkoxy, and the like, R4 and R5 independently represent hydrogen, alkyl, aryl, or the like; and n represents 0, 1, or 2).    Patent Document 1: JP-A-2821233    Patent Document 2: Pamphlet of International Patent Publication WO 99/01416    Patent Document 3: Pamphlet of International Patent Publication WO 2006/033318    Patent Document 4: Pamphlet of International Patent Publication WO 95/18617